Inn-Chi Lee1, Jiann-Jou Yang2, Shuan-Yow Li3. 1. Division of Pediatric Neurology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan. Electronic address: y610@mercury.csmu.edu.tw. 2. Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Genetics Laboratory and Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan. 3. Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Genetics Laboratory and Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan. Electronic address: i0000528@ms12.hinet.net.
Abstract
BACKGROUND/ PURPOSE: Pediatric epilepsy caused by a KCNQ2 gene mutation usually manifests as benign familial neonatal seizures (BFNS) during the 1st week of life. However, the exact mechanism, phenotype, and genotype of the KCNQ2 mutation are unclear. METHODS: We studied the KCNQ2 genotype from 75 nonconsanguineous patients with childhood epilepsy without an identified cause (age range: from 2 days to 18 years) and from 55 healthy adult controls without epilepsy. KCNQ2 mutation variants were transfected into HEK293 cells to investigate what functional changes they induced. RESULTS: Four (5%) of the patients had the E515D KCNQ2 mutation, which the computer-based PolyPhen algorithm predicted to be deleterious. Their seizure outcomes were favorable, but three had an intellectual disability. Two patients with E515D presented with continuous spikes and waves during slow-wave sleep (CSWS), and the other two presented with BFNS. We also analyzed 10 affected family members with the same KCNQ2 mutation: all had epilepsy (8 had BFNS and 2 had CSWS). A functional analysis showed that the recordings of the E515D currents were significantly different (p<0.05), which suggested that channels with KCNQ2 E515D variants are less sensitive to voltage and require stronger depolarization to reach opening probabilities than those with the wild type or N780T (a benign polymorphism). CONCLUSION: KCNQ2 mutations can cause various phenotypes in children: they lead to BFNS and CSWS. We hypothesize that patients with the KCNQ2 E515D mutation are susceptible to seizures.
BACKGROUND/ PURPOSE: Pediatric epilepsy caused by a KCNQ2 gene mutation usually manifests as benign familial neonatal seizures (BFNS) during the 1st week of life. However, the exact mechanism, phenotype, and genotype of the KCNQ2 mutation are unclear. METHODS: We studied the KCNQ2 genotype from 75 nonconsanguineous patients with childhood epilepsy without an identified cause (age range: from 2 days to 18 years) and from 55 healthy adult controls without epilepsy. KCNQ2 mutation variants were transfected into HEK293 cells to investigate what functional changes they induced. RESULTS: Four (5%) of the patients had the E515DKCNQ2 mutation, which the computer-based PolyPhen algorithm predicted to be deleterious. Their seizure outcomes were favorable, but three had an intellectual disability. Two patients with E515D presented with continuous spikes and waves during slow-wave sleep (CSWS), and the other two presented with BFNS. We also analyzed 10 affected family members with the same KCNQ2 mutation: all had epilepsy (8 had BFNS and 2 had CSWS). A functional analysis showed that the recordings of the E515D currents were significantly different (p<0.05), which suggested that channels with KCNQ2E515D variants are less sensitive to voltage and require stronger depolarization to reach opening probabilities than those with the wild type or N780T (a benign polymorphism). CONCLUSION:KCNQ2 mutations can cause various phenotypes in children: they lead to BFNS and CSWS. We hypothesize that patients with the KCNQ2E515D mutation are susceptible to seizures.
Authors: Michael F Hammer; Atsushi Ishii; Laurel Johnstone; Alexander Tchourbanov; Branden Lau; Ryan Sprissler; Brian Hallmark; Miao Zhang; Jin Zhou; Joseph Watkins; Shinichi Hirose Journal: PLoS One Date: 2017-07-07 Impact factor: 3.240